Prognosis of stage III colorectal carcinomas with FOLFOX adjuvant chemotherapy can be predicted by molecular subtype

// Yujin Kwon 1, * , Minhee Park 1, * , Mi Jang 1, * , Seongju Yun 1 , Won Kyu Kim 1 , Sora Kim 2 , Soonmyung Paik 2 , Hyun Jung Lee 3 , Sungpil Hong 3 , Tae Il Kim 3 , Byungsoh Min 4 and Hoguen Kim 1 1 Department of Pathology and BK21 for Medical Science, Yonsei University College of Medicine, Seoul, Korea 2 Severance Biomedical Science Institute and BK21 for Medical Science, Yonsei University College of Medicine, Seoul, Korea 3 Department of Internal Medicine, Yonsei University College of Medicine, Seoul, Korea 4 Department of Surgery, Yonsei University College of Medicine, Seoul, Korea * These authors have contributed equally to this work Correspondence to: Hoguen Kim, email: hkyonsei@yuhs.ac Keywords: colon cancer, mRNA expression-based molecular classification, molecular subtype, consensus molecular subtype, DNA microarray Received: September 02, 2016     Accepted: March 22, 2017     Published: April 11, 2017 ABSTRACT Individualizing adjuvant chemotherapy is important in patients with advanced colorectal cancers (CRCs), and the ability to identify molecular subtypes predictive of good prognosis for stage III CRCs after adjuvant chemotherapy could be highly beneficial. We performed microarray-based gene expression analysis on 101 fresh-frozen primary samples from patients with stage III CRCs treated with FOLFOX adjuvant chemotherapy and 35 matched non-neoplastic mucosal tissues. CRC samples were classified into four molecular subtypes using nonnegative matrix factorization, and for comparison, we also grouped CRC samples using the proposed consensus molecular subtypes (CMSs). Of the 101 cases, 80 were classified into a CMS group, which shows a 79% correlation between the CMS classification and our four molecular subtypes. We found that two of our subtypes showed significantly higher disease-free survival and overall survival than the others. Group 2, in particular, which showed no disease recurrence or death, was characterized by high microsatellite instability (MSI-H, 6/21), abundant mucin production (12/21), and right-sided location (12/21); this group strongly correlated with CMS1 (microsatellite instability immune type). We further identified the molecular characteristics of each group and selected 10 potential biomarker genes from each. When these were compared to the previously reported molecular classifier genes, we found that 31 out of 40 selected genes were matched with those previously reported. Our findings indicate that molecular classification can reveal specific molecular subtypes correlating with clinicopathologic features of CRCs and can have predictive value for the prognosis for stage III CRCs with FOLFOX adjuvant chemotherapy.